68 Ga-Galmydar: Biodistribution and radiation dosimetry studies in rodents

Jothilingam Sivapackiam, Richard Laforest, Vijay Sharma

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: 68 Ga-Galmydar is an avid transport substrate of ABCB1 (P-Glycoprotein; 170 kDa plasma membrane protein), breast cancer resistance protein (BCRP; ABCG2; 72 kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and localizes within the mitochondria of tumor and myocardium cells. 68 Ga-Galmydar excretes from blood pool quickly, and shows stable retention within rat myocardium in vivo for extended periods, therefore, the agent shows potential to enable myocardial perfusion imaging. The PET tracer also demonstrates ability to probe viability of the blood brain barrier (BBB) in WT mice compared with their mdr1a/1b (−/−) (dKO) and mdr1a/1b/ABCG2 (−/−/−) (t-KO) counterparts. Herein, we report dosimetry data for 68 Ga-Galmydar in mice, and extrapolate that information to determine effective dose (ED) for human studies. Methods: To further assess safety profiles of 68 Ga-Galmydar for enabling its deployment as a PET imaging probe for biomedical imaging in vivo, we estimated human radiation dosimetry extrapolated from mice biodistribution data. To accomplish this objective, 68 Ga-Galmydar was injected intravenously into tails, mice were euthanized, organs harvested (5 min, 15 min, 30 min, 60 min, 120 min), counted, radiation doses to each organ, and whole body were also determined. Results: The effective dose (ED) have been found to be 0.021 mGy/MBq in males and 0.023 mGy/MBq in females. The highest radiation dose was estimated to the kidneys with a value of 0.17 mGy/MBq for males and 0.19 mGy/MBq for females with contribution from activity in the urine prior to excretion. The critical organ in humans has been determined to be the gall bladder. These data provide preliminary projections on human dosimetry derived from rodent estimates thus providing platform for further validation of dosimetry analysis in human subjects. Conclusions: Combined data obtained from radiation dosimetry studies in mice indicate that 68 Ga-Galmydar would be safe for further evaluation of dosimetry toxicity and myocardial perfusion PET imaging in humans.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalNuclear Medicine and Biology
Volume59
DOIs
StatePublished - Apr 2018

Keywords

  • BCRP
  • Ga-Galmydar
  • Myocardial perfusion imaging
  • Pgp
  • Radiation dosimetry

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